ArticleJournal of medicinal chemistry2012
Identification of novel α4β2-nicotinic acetylcholine receptor (nAChR) agonists based on an isoxazole ether scaffold that demonstrate antidepressant-like activity.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 46 citations in OpenAlex.
- Neuropharmacology of Nicotine Addiction and Therapeutic Strategies for Smoking Cessation.Biology · 2026Review
- Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models.Acta pharmaceutica Sinica. B · 2021Article
- Sigma-1 Receptor Agonist TS-157 Improves Motor Functional Recovery by Promoting Neurite Outgrowth and pERK in Rats with Focal Cerebral Ischemia.Molecules (Basel, Switzerland) · 2021Article
- Pyrrolo[2',3':3,4]cyclohepta[1,2-Journal of medicinal chemistry · 2020Article
- Antimicrobial, Antioxidant, and Anticancer Activities of Some Novel Isoxazole Ring Containing Chalcone and Dihydropyrazole Derivatives.Molecules (Basel, Switzerland) · 2020Article
- The synthetic and therapeutic expedition of isoxazole and its analogs.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2018Review
- Recent developments in novel antidepressants targeting α4β2-nicotinic acetylcholine receptors.Journal of medicinal chemistry · 2014Review
- Pharmacokinetics and brain penetration of LF-3-88, (2-[5-[5-(2(S)-azetidinylmethoxyl)-3-pyridyl]-3-isoxazolyl]ethanol), a selective α4β2-nAChR partial agonist and promising antidepressant.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2013Article
- From α4β2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design.ACS medicinal chemistry letters · 2012Article
- The nicotinic acetylcholine receptor as a target for antidepressant drug development.TheScientificWorldJournal · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
There is considerable evidence to support the hypothesis that the blockade of nAChR is responsible for the antidepressant action of nicotinic ligands. The nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine, has been shown to be an effective add-on in patients that do not respond to selective serotonin reuptake inhibitors. This suggests that nAChR ligands may address an unmet clinical need by providing relief from depressive symptoms in refractory patients. In this study, a new series of nAChR ligands based on an isoxazole-ether scaffold have been designed and synthesized for binding and functional assays. Preliminary structure-activity relationship (SAR) efforts identified a lead compound 43, which possesses potent antidepressant-like activity (1 mg/kg, IP; 5 mg/kg, PO) in the classical mouse forced swim test. Early stage absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) studies also suggested favorable drug-like properties, and broad screening toward other common neurotransmitter receptors indicated that compound 43 is highly selective for nAChRs over the other 45 neurotransmitter receptors and transporters tested.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.